TY - JOUR
T1 - Cell death in the pathogenesis of heart disease
T2 - Mechanisms and significance
AU - Whelan, Russell S.
AU - Kaplinskiy, Vladimir
AU - Kitsis, Richard N.
PY - 2009/3/17
Y1 - 2009/3/17
N2 - Cell death was once viewed as unregulated. It is now clear that at least a portion of cell death is a regulated cell suicide process. This type of death can exhibit multiple morphologies. One of these, apoptosis, has long been recognized to be actively mediated, and many of its underlying mechanisms have been elucidated. Moreover, necrosis, the traditional example of unregulated cell death, is also regulated in some instances. Autophagy is usually a survival mechanism but can occur in association with cell death. Little is known, however, about how autophagic cells die. Apoptosis, necrosis, and autophagy occur in cardiac myocytes during myocardial infarction, ischemia/reperfusion, and heart failure. Pharmacological and genetic inhibition of apoptosis and necrosis lessens infarct size and improves cardiac function in these disorders. The roles of autophagy in ischemia/reperfusion and heart failure are unresolved. A better understanding of these processes and their interrelationships may allow for the development of novel therapies for the major heart syndromes.
AB - Cell death was once viewed as unregulated. It is now clear that at least a portion of cell death is a regulated cell suicide process. This type of death can exhibit multiple morphologies. One of these, apoptosis, has long been recognized to be actively mediated, and many of its underlying mechanisms have been elucidated. Moreover, necrosis, the traditional example of unregulated cell death, is also regulated in some instances. Autophagy is usually a survival mechanism but can occur in association with cell death. Little is known, however, about how autophagic cells die. Apoptosis, necrosis, and autophagy occur in cardiac myocytes during myocardial infarction, ischemia/reperfusion, and heart failure. Pharmacological and genetic inhibition of apoptosis and necrosis lessens infarct size and improves cardiac function in these disorders. The roles of autophagy in ischemia/reperfusion and heart failure are unresolved. A better understanding of these processes and their interrelationships may allow for the development of novel therapies for the major heart syndromes.
KW - Apoptosis
KW - Autophagic cell death
KW - Autophagy
KW - Cardiac remodeling
KW - Myocardial infarction
KW - Myocardial ischemia/reperfusion
KW - Necrosis
UR - http://www.scopus.com/inward/record.url?scp=77951901715&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77951901715&partnerID=8YFLogxK
U2 - 10.1146/annurev.physiol.010908.163111
DO - 10.1146/annurev.physiol.010908.163111
M3 - Review article
C2 - 20148665
AN - SCOPUS:77951901715
SN - 0066-4278
VL - 72
SP - 19
EP - 44
JO - Annual review of physiology
JF - Annual review of physiology
ER -